Long-term outcomes of surgical resection of the jaws in cancer patients with bisphosphonate-related osteonecrosis

Surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is controversial. Current recommendations contraindicate aggressive surgery because its results are unpredictable and may trigger disease progression. In this prospective study, we assessed the effectiveness of surgical resection of the jaws in cancer patients with BRONJ. Between June 2004 and July 2009, 30 cancer patients with refractory BRONJ underwent surgical resection of the jaws at our Units. They were followed-up weekly for the first month, at 3-month intervals up to 1 year, and at 6-month intervals up to 2 years. Panoramic radiographs and CT-scan were obtained at 3, 6, 12, 18 and 24 months. Primary outcomes were the 24-month recurrence rate of BRONJ and the 24-month mortality rate. Secondary outcomes were post-operative complications, duration of hospital stay after surgery, time to return to oral diet, and degree of oral pain. The 30 patients had a median age of 66 years and were mostly females (80%). Twenty-eight underwent a single resection and two had both jaws resected, for a total of 32 resected jaws. The cumulative recurrence rate of BRONJ in resected jaws 3.1% and 9.4% at 3 and 6 months, respectively. All the jaws with recurrent BRONJ had osteomyelitis at the margins of bone resection. The cumulative incidence of death was 3%, 12% and 16% at 12, 18 and 24 months. Surgical resection of BRONJ was highly effective, with few post-operative complications and were not associated with long-term mortality.     

New perspective on the nutritional approach to cancer-related anorexia/cachexia: preliminary results of a randomised phase III clinical trial with five different arms of treatment

Cancer-related anorexia/cachexia syndrome (CACS) is a multifactorial syndrome characterised by tissue wasting, particularly lean body mass (LBM), metabolic alterations, fatigue, anorexia and reduced food intake. In April 2005 we started a phase III randomised study to establish the most effective and safest treatment for CACS addressing as primary endpoints: LBM, resting energy expenditure (REE), total daily physical activity, interleukin (IL)-6 and tumour necrosis factor (TNF)-α levels, and fatigue. According to the statistical design the sample size was 475 patients (95 per arm). Eligibility criteria: histologically confirmed tumours of any site; weight loss −5% in the last 3 months and/or abnormal laboratory values; life expectancy >4 months. Patients were treated with either antineoplastic therapy or supportive care. All patients received as basic oral treatment polyphenols plus alpha lipoic acid plus carbocysteine plus vitamins A, C and E. Patients were then randomised to one of the following 5 arms: (1) medroxyprogesterone acetate (MPA)/megestrol acetate (MA); (2) pharmaconutritional support containing eicosapentaenoic acid (EPA); (3) l-carnitine; (4) thalidomide; and (5) a combination of all the above agents. Treatment duration was 4 months. Interim analyses were planned after every 100 randomised patients. In September 2008, 280 patients were randomised and 240 were evaluable: M/F 167/113, mean age 62 years (range 30-84), 96% stage IV. A first interim analysis on 125 patients showed a worsening of LBM, REE and fatigue in arm 2 in comparison to the others and therefore it was withdrawn from the study. A second interim analysis after the enrolment of 204 patients showed that arm 1 was clearly significantly less effective than the others for primary efficacy endpoints, therefore it was withdrawn from the study. Statistical analysis in September 2008 showed a significant improvement of LBM (by dual X-ray energy absorptiometry), REE and fatigue in arm 5, a decrease of IL-6 in arms 3 and 5, and a decrease of TNF-α in arms 3 and 4. As for toxicity, 1 patient discontinued MPA because of deep vein thrombosis and 1 patient discontinued L-carnitine because of severe diarrhoea. In conclusion, the interim results seem to suggest that the most effective treatment for cancer patients with CACS/oxidative stress (OS) should be the combination regimen. The study is in progress.     

Crucial Functionalizations of Carbon Nanotubes for Improved Drug Delivery: A Valuable Option?

Amidst the myriad of Drug Delivery Systems able to enhance delivery, absorption and intracellular uptake of a bioactive molecule while protecting it from deactivation, Carbon Nanotubes (CNTs) have emerged as a recent and promising option especially in cancer therapy. This is mainly due to their unique properties, which render them extremely versatile through the incorporation of several functional groups and targeting molecules at the same time, while their natural shape allows them to selectively penetrate across biological barriers in a non-invasive way. In this expert review we aim to evaluate whether this innovative material, once chemically-modified with suitable functionalizations, can be considered as a valuable system in comparison to the already existing nanodevices. This will include the estimation of the most recent advances in the field of nanotechnology, together with a cautious evaluation of potential risks and hazards associated with the extensive use of this fascinating, but still unknown, nanomaterial.     

Heart transplantation in a child with LGMD2I presenting as isolated dilated cardiomyopathy

Limb-girdle muscle dystrophy type 2I is associated with mutations in the gene encoding Fukutin-related protein. Clinical phenotypes are heterogeneous, ranging from isolated hyperCkemia to severe congenital muscular dystrophy. Affected patients frequently develop dilated cardiomyopathy, depending on evolution of their skeletal myopathy. We report on an 8 years-old boy presenting a severe dilated cardiomyopathy requiring heart transplantation. The child harbored a homozygous p.Leu276Ile mutation in Fukutin-related protein gene (FKRP). At the current age of 20 years, the patient shows persistent hyperCKemia but no clinical muscle weakness, CT scan showing very mild features of muscle involvement. Our findings add to the array of clinical presentations of FKRP mutations.     

The Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for juvenile systemic sclerosis

OBJECTIVE: To develop criteria for the classification of systemic sclerosis (SSc) in children (juvenile SSc). METHODS: The study consisted of 3 phases: 1) collection of data on the signs and symptoms of actual patients with juvenile SSc that are useful for defining involvement of a particular organ; 2) selection of the parameters essential for the classification of juvenile SSc and preparation of a set of provisional classification criteria (PCC) using 2 Delphi surveys; 3) consensus conference consisting of 2 steps: discussion and rating of clinical profiles of 160 patients with definite juvenile SSc, possible juvenile SSc, or other fibrosing diseases as "having or not having juvenile SSc," using nominal group technique, and defining those PCC with the best statistical performance and highest face validity by using the clinical profiles of patients with definite juvenile SSc as the gold standard. RESULTS: In phase 1, 55 centers submitted clinical data on 153 patients with juvenile SSc. A total of 48 signs and symptoms were derived from these patient data and were used to define 9 organ system categories (cutaneous, vascular, gastrointestinal, respiratory, renal, cardiac, neurologic, musculoskeletal, and serologic). During phase 2, these were reduced to 21 criteria (3 major criteria [Raynaud's phenomenon, proximal skin sclerosis/induration of the skin, and sclerodactyly] and 18 minor criteria) and combined to generate 86 different PCC. At the consensus conference, these 86 definitions were tested on the case profiles of 127 patients with juvenile SSc. The PCC with the highest ranking were proximal sclerosis/induration and at least 2 minor criteria. CONCLUSION: These provisional classification criteria for juvenile SSc will help standardize the conduct of clinical research, epidemiologic and outcome studies, and therapeutic trials.     

Sleep rebound attenuates context-dependent behavioural sensitization induced by amphetamine

We have recently demonstrated that paradoxical sleep deprivation (PSD) potentiates the induction of amphetamine (AMPH)-induced behavioural sensitization by increasing its conditioned component. In the present study, the effects of sleep rebound (induced by 24 h recovery period from PSD) were studied on AMPH-induced behavioural sensitization. Sleep rebound attenuated the acute locomotor-stimulating effect of AMPH. AMPH-induced behavioural sensitization was context-specific and was also attenuated by sleep rebound. These results strengthen the notion that sleep conditions can influence AMPH-induced behavioural sensitization.     

Circumumbilical pyloromyotomy in the era of minimally invasive surgery

Background/purpose

No studies have investigated the cosmetic outcome of current approaches to pyloromyotomy in infants with hypertrophic pyloric stenosis. The purpose of this study was to evaluate the final appearance of the scar in patients undergoing circumumbilical pyloromyotomy.

Methods

During a 16-year period, 86 infants underwent circumumbilical pyloromyotomy at our institution. A detailed questionnaire was created to document the family members' perceptions of the esthetic appearance of the scar. Data were collected by telephone interview and at clinic visit. In addition, cosmesis was assessed by 5 staff members who scored blindly the esthetic outcome of the scars with comparative photographs, using a categorical scale.

Results

Fifty-seven families were tracked by telephone contact. In the family questionnaire, 100% of families reported an excellent or good scar. Of these, forty-one (72%) were available for cosmetic assessment. Follow-up ranged between 5 months and 15 years (mean, 6 years). The panel members ranked the scar, on average, as excellent or good for 90% of the patients. No assessor stated that a scar was unacceptable. Intra- and interobserver agreement was 0.72 and 0.78, respectively.

Conclusions

Overall satisfaction with the cosmetic outcome of circumumbilical pyloromyotomy is very high.     

The eyelid crease approach to angular dermoid cysts in pediatric general surgery

Purpose

We recently adopted an approach described by eyelid surgeons for angular dermoid cyst excision. The aim of this study was to compare the outcome of this technique with that accomplished through a conventional trans-eyebrow incision.

Methods

Prospective nonrandomized study of 34 consecutive children treated between January 2000 and December 2006. Twenty-six patients (group I) were operated on through a trans-eyebrow incision, whereas 8 (group II) received an upper eyelid crease incision. Performance measures included cosmesis, operative time, and complications. Cosmesis was assessed blindly with comparative photographs, using a 100-mm visual analog scale.

Results

No significant differences were found between groups I and II with regard to age at surgery (22 ± 17 vs 24 ± 4 months; P = .07) and operative time (42 ± 21 vs 40 ± 16 minutes; P = .9). In group II, the scar resulted invisible when the affected side was assessed with the eye open and still significantly better than group I, when evaluated with the eye closed (96 ± 7 vs 81 ± 18 mm; P = .0001). All patients and their families reported great satisfaction and an excellent scar. There were neither major postoperative complications nor recurrence of the lesion.

Conclusions

Angular dermoid cyst excision using an eyelid crease approach yields excellent cosmesis and represents a safe, simple, and easily reproducible procedure in pediatric general surgical practice.